Predominant role of toll-like receptor 2 versus 4 in Chlamydia pneumoniae-induced activation of dendritic cells

J Immunol. 2001 Sep 15;167(6):3316-23. doi: 10.4049/jimmunol.167.6.3316.

Abstract

Chlamydia pneumoniae is an obligate intracellular human pathogen causing diseases such as pneumonia, bronchitis, and pharyngitis. Because of its intracellular replication, cell-mediated immune responses are needed to mediate successful defenses of the host. Because dendritic cells play a central role in linking innate immunity and Ag-specific cell-mediated immune responses we asked whether dendritic cells are activated upon contact with C. pneumoniae and whether known Toll like receptors (TLR) are involved in this process. Here we show that C. pneumoniae was taken up by bone marrow-derived murine dendritic cells. Ingested C. pneumoniae appeared to be unable to develop mature inclusion inside dendritic cells. Furthermore, upon contact with C. pneumoniae dendritic cells were potently stimulated because NF-kappaB was activated and translocated to the nucleus, cytokines like IL-12p40 and TNF-alpha were secreted, and expression of MHC class II molecules, CD40, CD80, and CD86 was up-regulated. Importantly, secretion of cytokines as well as translocation of NF-kappaB were dependent on the presence of TLR2 and independent from TLR4 with the exception of IL-12p40 secretion, which was attenuated in the absence of either a functional TLR2 or 4. In conclusion, we show here that recognition of the Gram-negative bacterium C. pneumoniae depends largely on TLR2 and only to a minor extent on TLR4.

Publication types

  • Comparative Study

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Bone Marrow Cells / immunology
  • Cell Line
  • Cells, Cultured
  • Chlamydophila pneumoniae / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / microbiology
  • Drosophila Proteins*
  • Gene Expression Regulation
  • Genes, Reporter
  • Humans
  • Interleukin-12 / metabolism
  • Kidney
  • Luciferases / analysis
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal
  • NF-kappa B / physiology
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Specific Pathogen-Free Organisms
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Transcription, Genetic
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Antigens, CD
  • Drosophila Proteins
  • Membrane Glycoproteins
  • NF-kappa B
  • Receptors, Cell Surface
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Luciferases